FDA Draft Guidance Clarifies Recommendations for Distribution of Scientific and Medical Publications on Off-Label Use

FDA Draft Guidance Clarifies Recommendations for Distribution of Scientific and Medical Publications on Off-Label Use

FDA has issued draft guidance revising its 2009 guidance on manufacturers' dissemination of "journal articles" and "scientific or medical reference publications" that address unapproved or "off-label" uses of drugs and devices. The new draft guidance broadens the scope and description of its recommended practices by including the dissemination of (i) Clinical Practice Guidelines ("CPGs") and (ii) chapters of medical texts and sections of CPGs rather than the entire publication.

Congress has long recognized that requiring that each indication and intended use of a drug or device be proven safe and effective is critical to the protection of the public health.[1] Under the Food, Drug, and Cosmetic Act ("FDCA"), drugs and devices that are intended by the manufacturer for an unapproved use, or are accompanied by material that suggests an unapproved use, may be considered adulterated and/or misbranded.[2] Nevertheless, physicians may prescribe or use drugs or devices off-label, if they deem it appropriate in the exercise of their professional judgment in making individual patient-care decisions. There is significant concern, however, that some such uses may be based on anecdotal evidence or preliminary study, rather than rigorous, well-controlled, and replicated scientific studies.

FDA states that it is now revising its 2009 guidance[3] in response to stakeholder questions about its application to scientific and medical reference texts, as well as CPGs, that include information on off-label uses. Unlike the previous iteration, this draft guidance provides recommendations for journal articles, reference texts, and CPGs in three separate sections, tailored to each type of publication. In addition, the draft guidance separately addresses reference texts and CPGs distributed in their entirety and by chapter or section, respectively. Consistent with longstanding FDA policy and practice, the upshot of this new draft guidance is that if manufacturers distribute such information as recommended, FDA does not intend to use the distribution as evidence of the manufacturer's intent for the product to be used off-label.

The draft guidance addresses journal articles, reference texts, and CPGs in three sections, which are very similar and share the same general approach, and provides lists regarding what a manufacturer "should" do as well as what the publication "should," "should not," and "must not" include. The lists, in some instances, include additional characterization of the bulleted item to further explain the Agency's intent.

Newly incorporated to the draft guidance document is the concept of CPGs. FDA notes that CPGs include recommendations intended to help clinicians make decisions for individual patient care, including circumstances where there are few or no approved products or the approved products have not proven successful for the patient. The draft guidance treats CPGs similarly to journal articles, except distinctions are made depending on whether a CPG is disseminated in its entirety or by section. Like reference texts, FDA states that because CPGs are considerably longer than journal articles and generally address a wider range of topics, the recommendations for CPGs should differ somewhat from the recommendations for journal articles.

FDA also notes that its recommendations incorporate the standard of the Institute of Medicine ("IOM") for CPG "trustworthiness."[4] Among other things, the draft guidance states that manufacturers should distribute only a CPG that includes information on off-label uses if the CPG is "trustworthy," meaning it should be based on a systematic review of the evidence; be developed by experts in the field; consider patient subgroups and preferences; be based on a transparent process; clearly explain the relationships between care and outcomes and provide clear care recommendations including ratings of their quality and strength; and be considered and revised when and as warranted by new evidence.

FDA proposes revising its "current thinking" on recommended practices that drug and medical device manufacturers and their representatives should follow when distributing journal articles, reference texts, or CPGs that discuss unapproved new uses for approved drugs or approved or cleared medical devices marketed in the United States to health care professionals or health care entities. The 60-day comment period ends on May 2.

A copy of the draft guidance document is available here.

A copy of the Federal Register Notice announcing the availability of the draft guidance for industry on "Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended Practices" is available here.

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[1] This requirement was made part of the FDCA in 1962 by the Kefauver-Harris Amendments. See Pub.L. No. 87-781, 76 Stat. 780 (1962).

[2] See 21 U.S.C. §§ 321 (m)&(p); 331 (d), 351(f)(1), 352(f), 355(a), 352(o), 360c(f)(1), 360(e).

[3] The 2009 guidance is available here.

[4] The Medicare Improvements for Patients and Providers Act of 2008 required the Secretary of Health and Human Services to contract with IOM to undertake a study on "the best methods used in developing clinical practice guidelines." See Pub. L. No. 110-275, 122 Stat. 2595. The resulting report included standards for CPG "trustworthiness." See R. Graham, et al., Institute of Medicine of the National Academies, Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Clinical Practice Guidelines We Can Trust (2011).